We have investigated the effects of interferon-α (IFN-α) and 5-fluorouracil (5-FU) on meningioma cells in two different culture systems, evaluated by the uptake of radiolabelled methionine. With both IFN-α and 5-FU an inhibitory effect on the uptake of radiolabelled methionine by the meningioma cells was demonstrated, and we found a synergistic inhibitory effect with a combination of IFN-α and 5-FU. To obtain a maximal inhibition of cell metabolism without causing cell toxicity, we were able to decrease the dose of 5-FU by simultaneously adding IFN-α. Our results suggest that a combined treatment of IFN-α and 5-FU may be a successful alternative for patients with inoperable meningiomas. A novel in vitro positron emission tomography technique was used for the study of metabolic changes in tumour cells caused by drug treatment, which is complementary to conventional cell culture techniques.. ...
In this study, we systematically explored drug combinations to evaluate specific and promiscuous models of drug synergy. We developed a sensitive drug interaction classification assay and used it to find 38 synergistic drug pairs, of which only 1 (Terbinafine-Rapamycin) had been previously reported (Lehar et al, 2007).. To identify cases of specific synergy, predicted by synergistic genetic interaction, we integrated a newly assembled catalog of drug targets with the synergistic genetic interaction network. Although we tested 38 drug pairs corresponding to genetic interactions and found 14 (37%) to be synergistic, it is difficult to assess whether these drug synergies are better explained by genetic interaction or promiscuous synergy. Indeed, after accounting for background rates of synergy for each drug, our results did not show a significant enrichment for drug synergy among drugs targeting the products of genetically interacting genes.. There are many potential explanations for this ...
TY - JOUR. T1 - Divergent synergic effects in carcinogenesis initiation by simultaneous exposure to two genotoxic carcinogens. AU - Verdina, A.. AU - Zito, R.. AU - Federico, A.. AU - Falasca, G.. AU - Galati, R.. PY - 2000. Y1 - 2000. N2 - Carcinogenesis is a complex and multistep process starting from initiation to tumor progression. Synergistic mechanisms can occur at every step of the process. The aim of this work was to provide information about the effect of chemical carcinogens which, if administered in combination, result in positive as well as negative synergistic effects. In order to evaluate whether for some carcinogens synergism occurs at the initiation step, we compared the effects of Ethylmethanesulfonate (EMS) on Benzo[a]pyrene (BP)-DNA adducts formation in the liver and lung of male Swiss mice treated for seven days by i.p. dose of EMS (1.2 mg/Kg b.w.) alone or by simultaneous administration of three doses of BP (25, 50, 100 mg/Kg b.w.) injected i.p. or the first day of ...
TY - JOUR. T1 - Dual-mode nanoparticle probes for high-performance magnetic resonance and fluorescence imaging of neuroblastoma. AU - Lee, Jae Hyun. AU - Jun, Young Wook. AU - Yeon, Soo In. AU - Shin, Jeon Soo. AU - Cheon, Jinwoo. PY - 2006/12/11. Y1 - 2006/12/11. N2 - Working together: A "core-satellite" hybrid nanoparticle probe provides highly improved fluorescence and magnetic resonance (MR) imaging capabilities through synergistic enhancement of its respective components. These hybrid nanoprobes can be used for dual-modal fluorescence and MR imaging of neuroblastoma with expressed polysialic acids.. AB - Working together: A "core-satellite" hybrid nanoparticle probe provides highly improved fluorescence and magnetic resonance (MR) imaging capabilities through synergistic enhancement of its respective components. These hybrid nanoprobes can be used for dual-modal fluorescence and MR imaging of neuroblastoma with expressed polysialic acids.. UR - ...
The results showed: i) that both PC3 and LNCaP are sensitive to single and combination treatments regardless of hormone sensitivity status, ii) that treatment induced dual death pathways (apoptosis and necrosis) in both cell types, iii) that growth inhibition in both cell types correlated positively with cell death via apoptosis at lower drug concentrations and necrosis at higher concentrations, iv) that combination of genistein and beta-lapachone had synergistic inhibitory effects on growth and proliferation in both cell types ...
Aberrant growth factor production is a prevalent mechanism in tumourigenesis. If T-cells responded positively to a cancer-derived cytokine, this might result in selective enhancement of function within the tumour microenvironment. Here, we have chosen colony-stimulating factor-1 (CSF-1) as a candidate to test this concept. CSF-1 is greatly overproduced in many cancers but has no direct effects upon T-lymphocytes, which do not express the c-fms-encoded CSF-1 receptor. To confer CSF-1-responsiveness, we have expressed the human c fins gene in immortalized and primary T-cells. Addition of soluble CSF-1 resulted in synergistic enhancement of IL-2-driven T-cell proliferation. CSF-1 also co-stimulated the production of interferon (IFN)-gamma by activated T-cells. These effects required Y809 of the CSF-1R and activation of the Ras-MEK-MAP kinase cascade, but were independent of PI3K signalling. T-cells that express c-fins are also responsive to membrane-anchored CSF-1 (mCSF-1) which, unlike its soluble ...
Melinamide in combination with either retinol or retinyl ester resulted in a synergistic enhancement in keratinocyte proliferation. The effects of the retinol or retinyl esters in combination with fatty acid amides were analogous to treatment with retinoic acid.
Fig. 7. Comparison of the effect of RAD51 antisense molecule and RAD51 inhibitor IBR2 on the cytotoxicity of olaparib and other anticancer drugs. (A, C, and D) Cells were cultured in 25-cm2 flasks, and exposed to siRNA as described in Materials and Methods for 4 hours, followed by addition of one volume of medium. After a further 20 hours, the medium was changed and the drug indicated was added to the final desired concentration. The proliferation of cells in the presence of the indicated concentration of siRNA, as a percentage of the scrambled siRNA control, in (A) was 85.3% ± 11.0% (n = 9) for A549b and 70.2% ± 11.9% (7) for HT-29. In (C and D) the proliferation was 51.8% ± 12.7% (8) for A549b and 62.4% ± 11.6% (9) for DU145. (B) A549b cells were grown in 96-well plates and treated with simultaneous exposure to IBR2 and olaparib at the concentrations indicated. The relative cell density was determined after 4 days by viability staining. The relative density of cells treated with both ...
High expression levels of Inhibitors of Apoptosis Proteins (IAPs) have been correlated with poor cancer prognosis and block the cell death pathway by interfering with caspase activation. SMAC-mimetics are small-molecule inhibitors of IAPs that mimic the endogenous SMAC and promote the induction of cell death by neutralizing IAPs. In this study, anti-tumour activity of new SMAC-mimetics Birinapant and AT-406 is evaluated against colorectal adenocarcinoma cells and IAP cross-talk with either oncogenic BRAF or BCL-2, or with the TRAIL are further exploited towards rational combined protocols. It is shown that pre-treatment of SMAC-mimetics followed by their combined treatment with BRAF inhibitors can decrease cell viability, migration and can very efficiently sensitize colorectal tumour cells to apoptosis. Moreover, co-treatment of TRAIL with SMAC-mimetics can efficiently sensitize resistant tumour cells to apoptosis synergistically, as shown by median effect analysis. Finally, Birinapant and AT-406 can
In Response: Ropero et al. (1) conducted an evaluation of the combination of Herceptin and tamoxifen with analyses of drug interaction, the conclusions of which partially contradict our findings previously reported in this journal (3). Similar to our results, they found the drug combination to give a greater growth-inhibitory effect than either agent alone using breast cancer cells in culture. However, using similar pharmacologic analyses of drug interactions, we found the combination to give synergistic growth inhibition, whereas Ropero et al. found the combination to have an antagonistic interaction at doses corresponding to the IC30. Both studies used estrogen receptor-positive, HER2-overexpressing BT-474 human breast carcinoma cells, and it seems that biological differences in the cells used, as well as differences in some of the experimental details, likely account for the disparate outcomes of drug interaction analysis.. Vázquez-Martín et al. comment on our modeling of drug interactions. ...
Combination with other small molecule drugs represents a promising strategy to improve therapeutic efficacy of FLT3 inhibitors in the clinic. We demonstrated that combining ABT-869, a FLT3 inhibitor, with SAHA, a HDAC inhibitor, led to synergistic killing of the AML cells with FLT3 mutations and suppression of colony formation. We identified a core gene signature that is uniquely induced by the combination treatment in 2 different leukemia cell lines. Among these, we showed that downregulation of PTP4A3 (PRL-3) played a role in this synergism. PRL-3 is downstream of FLT3 signaling and ectopic expression of PRL-3 conferred therapeutic resistance through upregulation of STAT (signal transducers and activators of transcription) pathway activity and anti-apoptotic Mcl-1 protein. PRL-3 interacts with HDAC4 and SAHA downregulates PRL-3 via a proteasome dependent pathway. In addition, PRL-3 protein was identified in 47% of AML cases, but was absent in myeloid cells in normal bone marrows. Our results ...
Historically, understanding of acquired resistance (AQR) to combination treatment has been based on knowledge of resistance to its component agents. To test whether an altered drug interaction could be an additional factor in AQR to combination treatment, models of AQR to combination and single agent MEK and PI3K inhibitor treatment were generated. Combination indices indicated combination treatment of PI3K and MEK inhibitors remained synergistic in cells with AQR to single agent but not combination AQR cells. Differences were also observed between the models in cellular phenotypes, pathway signaling and drug cross-resistance. Genomics implicated TGFB2-EDN1 overexpression as candidate determinants in models of AQR to combination treatment. Supplementation of endothelin in parental cells converted synergism to antagonism. Silencing of TGFB2 or EDN1 in cells with AQR conferred synergy between PI3K and MEK inhibitor. These results highlight that AQR to combination treatment may develop through ...
Novel treatment trend for cancer - Combining radiotherapy and immunotherapy synergistically enhances local and systemic tumor control.
The present invention relates to synergistic combinations of immunostimulatory CpG oligonucleotides and immunopotentiating cytokines. In particular, the invention relates to methods of stimulating an immune response using the synergistic combination of compounds and products related thereto.
does anyone know of any drug combinations that show synergistic effects on mcf-7, or other breat cancer cell lines? thanks!. ...
Scheithauer, W., Temsch, E.M., Jakesz, R. (1987) Preclinical evaluation of synergistic drug combinations of mitoxantrone potentially active against human colorectal and gastric adenocarcinoma. In: Progress in Antimicrobial and Anticancer Chemotherapy. Ecomed Verlag, Landsberg, BRD, pp. 814-816 ...
Small molecule inhibitors of signal transduction pathways can elicit complex and sometimes non-intuitive molecular responses in cancer cells. Increasing evidence supports the notion that these responses are important mediators of de novo drug resistance. We systematically assessed molecular and cellular responses to MEK inhibitors, aiming at identifying meaningful targets for combination therapies. Proteomic analyses revealed an EGFR-dependent feedback loop resulting in activation of the PI3 kinase pathway following MEK inhibition. In agreement with this, combinations of MEK inhibitors and inhibitors of EGFR inhibitors or PI3 kinase show synergistic effects on cell proliferation and apoptosis rates in molecularly defined disease subtypes. To further explore molecular networks affected by MEK inhibition, Bayesian network inference algorithms were applied and reverse-engineered networks were generated that are amenable to in silico forward-simulation. Using this technology, new, MEK-dependent, ...
Today the norm in modern cancer treatment is to use different forms of drug combinations. Recently anti-cancer treatment using drug combinations has gained increased attention due to the outstanding pharmacotherapeutic opportunities provided by combination therapies. However, the potential of this field is largely unexplored, partly due to the complexities associated with the astronomical number of possible combinations and partly due to the lack of means for quantifying clinically relevant adverse side effects in the early stages of the combination discovery and development process. This has resulted in relatively limited progress in this area. Motivated by this unfortunate state-of-affairs, the research reported in this thesis was aimed at developing and implementing computational and experimental methods to facilitate and accelerate the discovery and development of anti-cancer therapies. In paper I, the largely overlooked concept of therapeutic synergy is re-introduced and demonstrated to be ...
Greenmedinfo.com - Natural Health Resource - The worlds most widely referenced, open access, natural medicine database, with 30,000+ study abstracts and growing daily
These so-called epigenetic therapy drugs, used together, achieved robust anti-tumor responses in human cancer cell lines and mice.
On the Functional Recovery Mechanism of the Cerebral Nervous System in Diabetic State under the Combination Effect of Exercise and Medication
On the Functional Recovery Mechanism of the Cerebral Nervous System in Diabetic State under the Combination Effect of Exercise and Medication
Biocidin® is a synergistic combination of botanical medicines which targets the entire GI tract and supports microbiome balance for healthy digestion and elimination.
Buy HEAVY DUTY - 90 caps Online.Heavy Duty Muscle Army is a powerful formula with 12 bioactive components the synergistic combination of which helps to keep the bones and teeth healthy; to the absorption of calcium and phosphorous; th
Definition of synergism: Interaction between two or more agents, entities, factors, or substances that produces an effect greater than the sum of their individual effects. Also called synergetic effect or synergistic effect, ...
Observe the colonies on your plate, comparing any differences in the appearance of the colony growth of each isolate, alone vs mixed. Look first at each control culture: the inoculum in each of the diagonal spots is a pure culture control as are the spots in the column on the far left. Compare each "spot" where two isolates are mixed to the control spots where each isolate is growing alone. Is either isolate growing better in combination than alone? If so, you have found a beneficial interaction. For example, in the assay shown above, it appears that 2+4 grows better than either 2 does alone, a positive interaction for isolate 2. Its hard to say what the presence of 2 does for 4 since isolate 2s heavy growth is making it hard to see what 4 is doing when in combo with 2. In contrast, isolates 2+8 appear to be grow equally well in combination as they do separately. We would not assess their relationship as either beneficial or antagonistic. Check carefully for combinations that show an ...
I just posted a HyGrid piece. And I checked my old pieces. My last one was 9 years ago.. I didnt think it had been that long ...
Dedifferentiated liposarcoma (DDLS) is a rare but aggressive cancer with high recurrence and low response rates to targeted therapies. Increasing treatment efficacy may require combinations of targeted agents that counteract the effects of multiple abnormalities. To identify a possible multicomponent therapy, we performed a combinatorial drug screen in a DDLS-derived cell line and identified cyclin-dependent kinase 4 (CDK4) and insulin-like growth factor 1 receptor (IGF1R) as synergistic drug targets. We measured the phosphorylation of multiple proteins and cell viability in response to systematic drug combinations and derived computational models of the signaling network. These models predict that the observed synergy in reducing cell viability with CDK4 and IGF1R inhibitors depends on the activity of the AKT pathway. Experiments confirmed that combined inhibition of CDK4 and IGF1R cooperatively suppresses the activation of proteins within the AKT pathway. Consistent with these findings, ...
2205 HER-2/neu and estrogen receptor (ER) play critical roles in breast cancer. HER-2/neu and ER are validated therapeutic targets; the anti-HER-2/neu antibody Herceptin and the antiestrogen tamoxifen are effective drugs targeting these two receptors. Retinoids have also been shown to inhibit breast cancer growth. We find that all-trans retinoic acid (atRA) downregulates phosphorylation of HER-2/neu and decreases ER activity in BT-474 human breast cancer cells. We thus hypothesize that treatment with atRA and simultaneous targeting of HER-2/neu and/or ER may synergistically inhibit growth of breast cancer cells. We find that combining atRA with Herceptin, tamoxifen, or both results in strong synergistic growth inhibition of BT-474 breast cancer cells. To elucidate the molecular mechanisms underlying this synergistic growth inhibition, we examined the effects of these various drug combinations on cell cycle and apoptosis. We find that atRA, Herceptin, and tamoxifen all lead to an enhanced ...
Learning from nature: The development of an MoS2/Ta3N5 nanocomposite as a catalyst for selective aerobic oxidation by O2 activation was inspired by the nitrogenase enzymes in nature. The superior performance of this biomimetic catalyst, which shows potential for the selective oxidation of multifunctional substrates (see picture), results from the integration of Ta3N5 and MoS2 at the nanoscale and the synergistic enhancement of their activity. ...
Ideally, drug interactions are scored from a checkerboard assay relative to the simple null model, indicating that the interaction of a drug with itself is additive (14, 15). Thus, with the Loewe additivity model, if a combinations effect is higher or lower than additivity, the combination is synergistic or antagonistic, respectively (Fig. 1A). We may visualize this intuitive interpretation of the checkerboard by evaluating the contour of a common phenotype (isobole). A straight contour indicates additivity, whereas concave and convex contours are observed in synergistic and antagonistic interactions, respectively (Fig. 1A). The shape of this curve is quantified using the fractional inhibitory concentration (FIC), the standard metric of interaction scores. In the absence of an efficient checkerboard assay, the Bliss multiplicative model has become a commonly used scoring system for determining drug interactions. The Bliss multiplicative model defines the expected phenotype [such as median ...
A high-risk group of patients with follicular lymphoma could benefit from a novel drug combination, according to a new study published in the Journal of Experimental Medicine.
With the emergence of multidrug-resistant organisms, combining medicinal plants with synthetic or orthodox medicines against resistant bacteria becomes necessary. In this study, interactions between methanolic extract of Acacia mearnsii and eight antibiotics were investigated by agar diffusion and checkerboard assays. The minimum inhibitory concentrations (MICs) of all the antibiotics ranged between 0.020 and 500 µg/mL while that of the crude extract varied between 0.156 and 1.25 mg/mL. The agar diffusion assay showed that extract-kanamycin combination had zones of inhibition ≥20 ± 1.0 mm in all the bacteria tested (100%), followed by extract-chloramphenicol (90%) | extract-ciprofloxacin = extract-tetracycline (70%) | extract-amoxicillin (60%) | extract-nalidixic acid (50%) | extract-erythromycin (40%) | extract-metronidazole (20%). The checkerboard showed synergistic interaction (61.25%), additivity/indifference (23.75%) and antagonistic (15%) effects. The synergistic interaction was most expressed
Results In line with robust T and B cell activation, IFN-γ, IFNα, CXCL13, IgG and IgM production was achieved by a combination of SEB and TLR9 (all at least p,0.001). LEF dose dependently inhibited B and T cell proliferation, Interferon, CXCL13 and immunoglobulin production. HCQ dose dependently inhibited B cell proliferation, IFN-α, CXCL13, and immunoglobulin production. T cell proliferation and IFN-γ production were inhibited by HCQ only at higher concentrations. At several suboptimal concentrations LEF and HCQ additively inhibited T cell proliferation both in healthy individuals and in pSS patients. (Figure 1). Significant additive effects were seen for all outcome measures except IFN-α. Since IFNa was already robustly inhibited by HCQ alone (eg.for pSS 90% at 3.3 μM, p,0.001), only trends towards additive effects were observed. ...
Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.. ...
The Skinceuticals Eye Balm helps you deal with collagen breakdowns, free radical damage and moisture loss. Rated at 4.6/5 by general public.
If you are a society or association member and require assistance with obtaining online access instructions please contact our Journal Customer Services team ...
5592 Abstract Although a number of methods for assessing drug interactions are available, most methods lack a means of selecting combinations of doses efficiently in planning such experiments. The power-maximized design, derived based on the uniform measures of all possible dose combinations of interest, is able to select the drug combinations (doses of each constituent drug) and to determine the required number of replicates at each combination in order to detect synergy, additivity or antagonism, with pre-specified statistical power for the experiment. An F-test is proposed to detect departures from additivity for combinations of two drugs. To explore the joint effect of the combination, a 3-dimensional combination index surface characterizes the interaction of a two-drug combination estimated using the B-splines. Synergism is manifested as a substantial drop in the combination index which is a 2-dimensional slice of the combination index surface. These methods were applied to evaluate SAHA ...
The scheduled delivery of synergistic drug combinations is increasingly recognized as highly effective against advanced solid tumors. Of particular interest are composite systems that release a sequence of drugs with defined kinetics and molar ratios to enhance therapeutic effect, while minimizing the dose to patie
Oncotarget | https://doi.org/10.18632/oncotarget.25480 Fiorella Vanderhoeven, Analía Lourdes Redondo, Ana Laura Martinez, Laura María Vargas-Roig, Angel Matias Sanchez, Marina Inés Flamini
GPs need to be aware of the bleeding risks associated with the use of chemotherapy or biological therapy alongside cancer drugs that restrict blood vessel growth, a US study suggests.
I have a protein-protein interaction that I have originally detected in bacterial two-hybrid system and pull-down experiments with bacterially expressed proteins also show positive interaction. Now I would like to confirm this interaction also in eukaryotic cells by coimmunoprecipitating the two. Since I do not have antibodies for these proteins, I am using GFP -(Bait) and HA-tagged (target) proteins and thus transfected cells. I have performed the experiment couple of times, and it kind of looks promising: I have positive interaction when the two proteins are present and all negative controls are negative. What makes me doubt is that I do not concentrate the target protein in the immunoprecipitation, that is that my band is weaker in the immunoprecipitation sample than in the original cell lysate sample. In order to have positive interaction do I have to be able to concentrate the target protein? So, what do you think, are these two proteins interacting ...
Drug synergy can be expressed not only as an additive effect, but also as potentiation, ie, substances combined effect is greater than the sum of effects of individual drugs.. In addition, allocate direct and indirect synergies, direct - drugs have a single point of application, an indirect - when the drugs have a different point of application and at the effect of indirectly affect each other.. additive method of drug therapy is widespread in modern medical practice, for example, the introduction of non-narcotic analgesics.Also found their other synergies.For example, the potentiation is used for the introduction of chlorpromazine and drugs for anesthesia.Chlorpromazine, providing a potentiating effect on drugs for anesthesia, to reduce their dosage.Indirect and indirect kinds of synergies are used to treat diabetes and asthma.. additive effect when used properly can be an excellent tool in the treatment of a large variety of diseases.At the same time it will help to heal even those diseases ...
The blog provides information of a general & public nature regarding national or other developments. None of the information contained herein is intended as legal advice or opinions relative to specific matters, facts, situations or issues. Additional facts, information or future developments may affect the subjects addressed in this blog. You should consult with an expert about your particular circumstances before acting on any of this information because it may not be applicable to your situation. This blog contains information and links to sites which are not owned or maintained by myself. I am not responsible for the content, linked sites, and the views expressed on linked sites do not necessarily reflect my views or opinions. The information contained herein is provided for personal, non-commercial, educational, entertainment and informational purposes only and does not constitute a guarantee of information or facts. I make no claims, expressed, implied, or statutory regarding the accuracy, ...
The goal of this clinical research study is to compare the safety and effectiveness of combining cytarabine with the study drug vosaroxin, versus cytarabine and a placebo, in treating patients with relapsed or refractory AML. Researchers want to compare how long these 2 study drug combinations may be able to help control the disease.
Vytorin is used in combination with proper diet to treat high cholesterol and triglyceride levels in the blood. This drug combination may help prevent medical problems caused...
Radiotherapy (RT), the major anti-cancer modality for more than half of cancer patients after diagnosis, has the advantage of local tumor control with relatively less systematic side effects comparing to chemotherapy. However, the efficacy of RT is limited by acquired tumor resistance leading to the risks of relapse and metastasis. To further enhance the efficacy of RT, with the renaissances of targeted immunotherapy (TIT), increasing interests are raised on RT combined with TIT including cancer vaccines, T-cell therapy, and antibody-based immune checkpoint blockers (ICB) such as anti-CTLA-4 and anti-PD1/PD-L1. In achieving a significant synergy between RT and TIT, the dynamics of radiation-induced response in tumor cells and stromal cells, especially the cross-talk between tumor cells and immune cells in the irradiated tumor microenvironment (ITME) as highlighted in recent literature are to be elucidated. The abscopal effect refereeing the RT-induced priming function outside of ITME could be ...
Fulltext - Comparative Evaluation of Zinc and Lead and their Synergistic Effects on Growth and Some Physiological Responses of Hassawi Okra (Hibiscus esculentus) Seedlings
https://doi.org/10.18632/oncotarget.3282 Ping Chen, Tao Hu, Yupei Liang, Yanan Jiang, Yongfu Pan, Chunjie Li, Ping Zhang, Dongping Wei, Pei Li, Lak Shin Jeong, Yiwei Chu, Hui Qi, Meng Yang, Robert...
Synergistic combination of trimetoprim and sulfamethoxazole, bacteriostatic active against many gram-negative and gram-positive bacteria.